rs753928772
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_000016.6(ACADM):c.1257C>A(p.Tyr419Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,592,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000016.6 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADM | NM_000016.6 | c.1257C>A | p.Tyr419Ter | stop_gained | 12/12 | ENST00000370841.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADM | ENST00000370841.9 | c.1257C>A | p.Tyr419Ter | stop_gained | 12/12 | 1 | NM_000016.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151836Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000364 AC: 9AN: 247506Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134208
GnomAD4 exome AF: 0.0000118 AC: 17AN: 1440292Hom.: 0 Cov.: 27 AF XY: 0.0000112 AC XY: 8AN XY: 717370
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151836Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74150
ClinVar
Submissions by phenotype
Medium-chain acyl-coenzyme A dehydrogenase deficiency Pathogenic:2Uncertain:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 13, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 27, 2022 | This sequence change creates a premature translational stop signal (p.Tyr419*) in the ACADM gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 3 amino acid(s) of the ACADM protein. This variant is present in population databases (rs753928772, gnomAD 0.08%). This premature translational stop signal has been observed in individual(s) with ACADM-related conditions (PMID: 32778825). ClinVar contains an entry for this variant (Variation ID: 488675). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects ACADM function (PMID: 24966162). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Likely pathogenic, no assertion criteria provided | clinical testing | Counsyl | Dec 26, 2018 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2020 | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 3 amino acids are lost; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 20036593) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at